The Immunopathology of Multiple Sclerosis: An Overview

  title={The Immunopathology of Multiple Sclerosis: An Overview},
  author={Hans Lassmann and Wolfgang Br{\"u}ck and Claudia F. Lucchinetti},
  journal={Brain Pathology},
Multiple sclerosis (MS) is traditionally seen as an inflammatory demyelinating disease, characterized by the formation of focal demyelinated plaques in the white matter of the central nervous system. In this review we describe recent evidence that the spectrum of MS pathology is much broader. This includes demyelination in the cortex and deep gray matter nuclei, as well as diffuse injury of the normal‐appearing white matter. The mechanisms responsible for the formation of focal lesions in… 
Multiple Sclerosis Pathology.
  • H. Lassmann
  • Biology, Medicine
    Cold Spring Harbor perspectives in medicine
  • 2018
The spectrum of MS lesions and their relation to the inflammatory process is described and it is suggested that inflammation drives tissue injury at all stages of the disease.
New findings and old controversies in the research of multiple sclerosis and its model experimental autoimmune encephalomyelitis
  • R. Aharoni
  • Biology, Psychology
    Expert review of clinical immunology
  • 2013
The interplay between inflammation and neurodegeneration mediating the disease, and therapeutic strategies attempting to induce immunomodulation and neuroprotective repair processes, are discussed.
Relapsing–remitting and primary progressive MS have the same cause(s) – the neuropathologist’s view: 1
The differences in the pathology between RRMS, SPMS and PPMS are of quantitative, but not of qualitative nature, and recent data suggest that oxidative injury and subsequent mitochondrial damage may play an important role in driving demyelination and neurodegeneration in the MS brain.
Exploring the origins of grey matter damage in multiple sclerosis
Histological, immunological and neuroimaging studies have provided new insight in this rapidly expanding field, and form the basis of the most recent hypotheses on the pathogenesis of grey matter damage.
Slowly Expanding Lesions
Chronic active lesions are thought to increase in size over time and may represent a mechanism for worsening in progressive MS, and may have different genetic underpinnings in white and gray matter.
Targets of the humoral autoimmune response in multiple sclerosis.
Progressive multiple sclerosis
It is shown that also in progressive MS, inflammation is the driving force for brain injury and that the discrepancy between inflammation-driven tissue injury and response to immunomodulatory therapies can be explained by different pathomechanisms acting in RRMS and progressive MS.
Inflammation in multiple sclerosis--sorting out the gray matter.
  • P. Calabresi
  • Medicine, Psychology
    The New England journal of medicine
  • 2011
The findings of the study by Lucchinetti et al provide definitive evidence that inflammatory disease of the gray matter commences early in the pathogenesis of some cases of multiple sclerosis.
Multiple sclerosis pathogenesis: missing pieces of an old puzzle
Findings of recent decades revealed several missing pieces of MS puzzle and showed that MS pathogenesis is more complex than the traditional view and may include: a primary degenerative process, generalized abnormality of normal-appearing brain tissue, pronounced gray matter pathology, involvement of innate immunity, and CD8 T cells and B cells.


Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination
At a given time point of the disease, the patterns of demyelination were heterogeneous between patients, but were homogenous within multiple active lesions from the same patient, suggesting that MS may be a disease with heterogeneous pathogenetic mechanisms.
Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion
Clinical and pathological findings in 12 patients with relapsing and remitting multiple sclerosis, who died during or shortly after the onset of a relapse, raise the possibility of some novel process underlying new lesion formation in multiple sclerosis.
Immunopathology of secondary‐progressive multiple sclerosis
Findings suggest that slowly expanding lesions (progressive plaques), in which ongoing myelin breakdown occurs in the absence of florid perivascular cell cuffing or other histological signs of acute inflammation, contribute to disease progression in cases of secondary‐progressive multiple sclerosis.
Axonal damage in acute multiple sclerosis lesions.
The results show the expression of amyloid precursor protein in damaged axons within acute multiple sclerosis lesions, and in the active borders of less acute lesions, which may have implications for the design and timing of therapeutic intervention.
Cortical demyelination and diffuse white matter injury in multiple sclerosis.
Global brain pathology in multiple sclerosis is analysed, focusing on the normal-appearing white matter (NAWM) and the cortex, to suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter.
Axonal transection in the lesions of multiple sclerosis.
Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.
A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica.
The extent of complement activation, eosinophilic infiltration and vascular fibrosis observed in the Devic NMO cases is more prominent compared with that in prototypic multiple sclerosis, and supports a role for humoral immunity in the pathogenesis of NMO.
Lesion development in Marburg's type of acute multiple sclerosis: from inflammation to demyelination
Findings from this single patient affirm that demyelination follows the migration of inflammatory cells from the circulation into the white matter with subsequent inflammation and demYelination.
Preferential Loss of Myelin‐Associated Glycoprotein Reflects Hypoxia‐Like White Matter Damage in Stroke and Inflammatory Brain Diseases
Brain white matter lesions presenting with MAG loss and apoptotic-like oligodendrocyte destruction, irrespective of their primary disease cause, revealed a prominent nuclear expression of hypoxia inducible factor-1α in various cell types, including oligodendedrocytes.